US2025368611A1PendingUtilityA1
Method for preparing beraprost 314-d sodium
Est. expiryMay 30, 2044(~17.8 yrs left)· nominal 20-yr term from priority
Inventors:Chang Young OhKee Young LeeSeung Jong LeeGanganna BogondaAreum BaekEunim JeongJodi CraigoTodd LorenzArthur P. BertolinoTeresa WhalenHeather Lynn Nottingham
C07C 67/317C07C 67/31C07C 68/02C07C 2601/10C07D 307/93A61P 29/00A61P 37/06A61K 31/343C07C 67/30C07C 69/734C07C 67/32
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Claims
Abstract
The present disclosure provides methods of synthesizing a compound of Formula I. The method proceeds through several different pathways including a radical cyclization. Also disclosed are compositions the compound of Formula I as well as methods of using the compound of Formula I in the treatment several conditions or disorders.
Claims
exact text as granted — not AI-modified1 . A method of preparing a product comprising a compound of Formula I having the structure:
wherein
R 1 is selected from H and a cation;
R 2 and R 3 are independently C 1-6 alkyl;
the method comprising the steps of:
(a) performing a condensation reaction on the compound
to form the compound
wherein R 4 is C(O)C 1-6 alkyl and R 5 is C 1-6 alkyl;
(b) coupling the carbonate of CPD-02 with
to form the compound
wherein is R 6 is C 1-6 alkyl and X is halide;
(c) hydrolyzing CPD-04 to form the compound
(d) protecting the alcohol of CPD-05 to form the compound
wherein R 7 is a hydroxy protecting group;
(e) performing a radical cyclization and trapping reaction on CPD-06 with
to form the compound
wherein R 8 and R 9 are independently C 1-6 alkyl; and
(f) converting CPD-08 to a compound of Formula I;
wherein the compound of Formula I is at least about 90% pure;
wherein the total amount of the impurities is in an amount of less than about 10.0%; and
wherein any individual impurity is present in an amount of less than about 1.0%.
2 . The method of claim 1 , further comprising cleaving the double bond of CPD-08 to from the compound
3 . The method of claim 2 , further comprising coupling CPD-09 with
to form the compound
4 . The method of claim 3 , further comprising reduction of the ketone of CPD-11 to form the compound
5 . The method of claim 4 , further comprising the deprotection of CPD-12 to form the compound
6 . The method of claim 5 , further comprising hydrolyzing CPD-12 to form the compound Formula I.
7 . The method of claim 1 , wherein R 1 is Na + .
8 . The method of claim 1 , wherein R 2 , R 3 , and R 6 are methyl.
9 . The method of claim 1 , wherein R 4 is C(O)Me.
10 . The method of claim 1 , wherein R 5 is ethyl.
11 . The method of claim 1 , wherein R 7 is tert-butyldimethylsilyl.
12 . The method of claim 1 , wherein R 8 is butyl.
13 . The method of claim 1 , wherein R 9 is pentyl.
14 . The method of claim 1 , wherein the compound of Formula I is:
15 . The method of claim 1 , wherein the method does not produce more than about 1.0% of an isomer other than the compound of Formula I.
16 . The method of claim 1 , wherein the method does not produce more than about 0.15% of an isomer other than the compound of Formula I.
17 . The method of claim 1 , wherein the method does not produce more than about 0.1% of an isomer other than the compound of Formula I.
18 . The method of claim 1 , wherein the method does not produce more than about 0.05% of an isomer other than the compound of Formula I.
19 . The method of claim 1 , wherein the compound of Formula I is at least about 95% pure.
20 . The method of claim 1 , wherein the compound of Formula I is at least about 99% pure.
21 . The method of claim 1 , wherein the compound of Formula I is at least about 99.8% pure.
22 . The method of claim 1 , wherein any individual impurity is present in an amount of less than about 0.15%.
23 . The method of claim 1 , wherein any individual impurity is present in an amount of less than about 0.1%.
24 . The method of claim 1 , wherein any individual impurity is present in an amount of less than about 0.05%.
25 . The method of claim 1 , wherein the compound of Formula I is prepared in an overall yield of at least about 5%.
26 . The method of claim 1 , wherein the compound of Formula I is prepared in an overall yield of at least about 10%.
27 . The method of claim 1 , wherein the total amount of the impurities is in an amount of less than about 5.0%.
28 . The method of claim 1 , wherein the total amount of the impurities is in an amount of less than about 1.0%.
29 . The method of claim 1 , wherein the total amount of the impurities is in an amount of less than about 0.2%.
30 . The method of claim 1 , wherein the impurity is selected from:
and a combination thereof.
31 . The method of claim 1 , wherein the impurity is selected from:
and a combination thereof.
32 . The method of claim 1 , wherein, Formula I is prepared without the use of chiral chromatography.
33 . The compound of claim 14 , wherein, sodium 4-((1R,2R,3aS,8bS)-2-hydroxy-1-((3S,4S,E)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-5-yl)butanoate is prepared without the use of chiral chromatography.
34 . A compound of the formula:
wherein
R 6 is C 1-6 alkyl;
R 7 is a hydroxy protecting group; and
X is halide.
35 . The compound of claim 32 , wherein the compound is:
36 .- 37 . (canceled)
38 . A method of treating cytokine release syndrome (CRS) in a subject, the method comprising administering to the subject a composition comprising an effective amount of the compound of Formula I or a pharmaceutically acceptable salt thereof according to claim 1 ; wherein the CRS is treated.
39 . (canceled)Join the waitlist — get patent alerts
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